A Cohn IV fraction of human plasma is being used as a source to purify somatomedin (SM). The material has been purified about 1000-fold by dialysis and ultrafiltration subsequent to acid treatment. Insulin contamination of the partially purified SM is removed by ion-exchange chromatography. The active principle, as measured by the uptake of 35S-Na2So4 by rat cartilage, is between 5000 to 12,000 daltons. Procedures are being developed to purify the SM further.